This proposal describes the development of an efficient synthesis of the pharmaceutical agents related to morphine. The major focus will be on the use of the intramolecular addition of enolates to pyridinium ions for the preparation of benzofuroisoquinolines, key morphine precursors, and the exploration of the efficient control of absolute stereochemistry which is possible due to the reversibility of this reaction. The conversion of the benzofuroisoquinolines into the morphine alkaloids will be addressed. New approaches to the morphine system will also be studied.